The long range goals of this laboratory focus on the neural mechanisms responsible for the generation and control of respiratory pattern. This project emphasizes the central neural connections and synaptic processing of many of the afferent systems which affect respiratory timing and motor patterns. The proposed experiments expand upon our previous findings concerning the nuclei and neurotransmitter receptor subtypes that are important in the processing of inspiratory inhibitory reflexes elicited by stimulation of the superior laryngeal nerve (SLN), intercostal nerve (ICN), vagus nerve (X), phrenic nerve (PN) and brainstem nuclei such as the dorsal (DRG), ventral (VRG) and pontine (PRG) respiratory groups. Stimulation of these inputs elicits an inspiratory termination and/or a transient attenuation of the motor output. Both of these inhibitory reflexes will be studied. Experiments will continue to investigate the role of brainstem nuclei in the processing of afferent inhibitory information. The specific aims to be examined include the: 1) role of the medial nucleus tractus solitarius (mNTS) in the transient inhibitions, 2) role of nitric oxide in NMDA-mediated responses to vagal reflexes, 3) second order neuronal projections in these reflexes, 4) role of these afferents/neurotransmitters in producing the breath-to-breath variability in respiratory pattern, and 5) role of the Pre-Botzinger Complex in the inspiratory termination reflexes. The mechanisms which affect respiratory pattern and rhythm are very important in the normal homeostatic response of the respiratory system to perturbations. Sleep, wakefulness, sneezing, coughing vomiting, postural changes, etc. are all important common behaviors that involve respiratory adaptations. Most of these perturbations involve afferent inputs that either initiate or modify the resultant motor program. These experiments will further our understanding of these connections and are likely to help elucidate the basic mechanisms involved in modulation of the central respiratory pattern generator. This will aid in understanding central respiratory disorders, including sudden infant death or the sleep apnea syndromes. We anticipate that the proposed experiments will yield important and useful information to our understanding of the basic mechanisms of respiratory control.